The purpose of the proposed 5-year career development award is to provide training in translational, patient oriented research at the postdoctoral level and to prepare the applicant for a leadership role in the fields of clinical research and molecular epidemiology. It is anticipated that the phased development plan will provide new and enhanced multidisciplinary skills in patient-oriented research, clinical trials, pharmacoepidemiology, molecular biology and statistical genetics, which will be later applied to the study of disease etiology and control. One of the strengths of the proposed development plan is the participation and commitment of four mentors, whose diverse and unique talents will influense the training of the applicant. Institutional support by Harvard School of Dental Medicine (responsible for training in cancer genetics), Harvard School of Public Health (pharmacoepidemiology and statistical genetics), the Massachusetts General Hospital Cancer Center (hands-on training in ethics and clinical trials) and Quintiles Corporation (training in clinical trials management, regulatory process and Good Clinical Practices) will ensure a plethora of educational resources and opportunities. This blend of academia, healthcare and research industry will provide for the specific skills required to a career devoted to clinical trials and epidemiolocic studies that utilize state-of-the-art molecular methods and findings. In his research, the investigator will directly interact with human subjects in an effort to identify environmental and genetic risk factors related to oral premalignancies. A case-control study will be conducted to investigate the association between oral premalignant lesions, genetic susceptibility markers and life-style risk factors (diet, alcohol and tobacco use) in greeks, a population who has traditionally exhibited very low oral cancer prevalence rates. Specifically, the investigators will study the effects of tobacco, alcohol, diet and polymorphisms at the Glutathione-S-Transerase T1 (GST-T) gene and Alcohol Dehydrogenase 3 (ADH3) gene. Impairment of an individual's ability to metabolize carcinogens properly may increase their bioavailability, and thus, inrease the probability of genetic damage of cell-cycle control regulators. An additional hypothesis to be evaluated is that p53 tumor suppressor gene mutations are more frequent in the lesions of patients with the GST-TO genotype than the GST-T1 genotype. Apart from contributing to the current body of knowledge about disease etiology, the proposed international collaborative investigation will provide the framework upon which the investigator will prepare for an independent research career.